Introduction: Lung cancer is still a major contributor to cancer mortality worldwide. More than 80–85% of cases are constituted by Non-Small Cell Lung Cancer (NSCLC), consisting of approximately 40% adenocarcinomas. The prevalence of T790M mutation also accounts for 30%–50% of resistance to first- and second-generation tyrosine kinase inhibitors (TKI) after 9-12 months of therapy. To overcome this health condition, osimertinib has emerged as a first-line target therapy for lung adenocarcinoma with Epidermal Growth Factor Receptor (EGFR) mutation. Therefore, this study aimed to determine the effectiveness of osimertinib administration as first-line therapy in adenocarcinoma patients with EGFR TKI mutation. Case Presentation: This study presented a case of 60-year-old woman with shortness of breath and cough accompanied by weight loss ± 10 kg in 3 months. Contrast chest MSCT (multislice computed tomography) scan showed a mass in the right lung accompanied by pleural and pericardial effusion. The results of the cytological examination of pleural fluid found a picture of adenocarcinoma. Furthermore, the diagnosis was continued by molecular examination of pleural fluid, and the results of the EGFR Exon 19 mutation were obtained. Based on the results of physical examination and several laboratory tests, a diagnosis of right pleural effusion and EGFR mutation lung adenocarcinoma was established.Conclusions: In this case, there was a clinical improvement after 8 months of osimertinib administration, along with enhancement in the control CT-SCAN. Osimertinib also showed the potential to extend progression-free survival by approximately 18.9 months compared to other generations of tyrosine kinase inhibitor therapy. This result was supported by the improvement of the clinical and performance status of patients in this case during osimertinib administration.